The general goal of the project is to explain how established drugs influence water and solute transport across simple epithelia. Research activities in this project period will focus on blood capillaries, where the principal modes of transport are believed to be filtration for water, unrestricted diffusion for lipid-soluble substances such as oxygen and radioxenon, and restricted diffusion for most small hydrophilic solutes. Carrier-mediated transport mechanisms exist at the blood-brain barrier but only for special classes of solutes that will not be used in this study. The capillary diffusion for inert reference solutes will be measured in skeletal muscle, heart and brain of anesthetized cats and/or rats. The goal is to identify physiological mechanisms that control transcapillary solute traffic and to elucidate how drugs and hormones modify these controls. Test drugs will include locally active vasoconstrictors and vasodilators. Possible sites of action are arterioles, precapillary sphincters, the capillary wall and the interstitium. Evidence will be sought for reversible drug effects on the capillary surface area available for exchange (functional capillary density) and on the diffusive conductances of the capillary wall and interstitial space (capillary permeability).